How to Improve Meniscal Repair through Biological Augmentation: A Narrative Review

Since the role of the menisci in knee stability, proprioception, and homeostasis has been well established, significant efforts have been made to repair meniscal tears, resulting in excellent clinical outcomes and a reduction in the progression of knee osteoarthritis (OA). However, varying failure rates have been reported, raising questions regarding the healing potential in cases of complex injuries, poorly vascularized and degenerated areas, and generally in the presence of unfavorable biological characteristics. Therefore, over the last few decades, different strategies have been described to increase the chances of meniscal healing. Biological augmentation of meniscal repair through various techniques represents a safe and effective strategy with proven clinical benefits. This approach could reduce the failure rate and expand the indications for meniscal repair. In the present study, we thoroughly reviewed the available evidence on meniscal repair surgery and summarized the main techniques that can be employed to enhance the biological healing potential of a meniscal lesion. Our aim was to provide an overview of the state of the art on meniscal repair and suggest the best techniques to reduce their failure rate.


Introduction
Meniscectomy was once a widely performed procedure [1][2][3][4] and considered the gold standard for treating symptomatic meniscal tears, offering good short-term clinical results, pain resolution, and functional improvement [5].However, recent studies have questioned the effectiveness of meniscectomy [2,[6][7][8][9].Good clinical outcomes depend on meticulous surgical indications, suggesting that partial meniscectomy should be reserved for patients with mechanical symptoms and unstable meniscal lesions on magnetic resonance imaging (MRI), or those who did not respond to conservative treatment [10].Additionally, arthroscopic meniscectomy has shown no superiority over sham surgery in cases of degenerative meniscopathy [9], and unsatisfactory results are to be expected if meniscectomy is performed without mechanical symptoms [11].It is also essential to differentiate between medial and lateral meniscectomy.While the former has been linked to better functional outcomes [12], the latter has been associated with an increased risk of chondrolysis [13,14] and less favorable clinical results [15].Furthermore, factors such as the integrity of the meniscal roots, lower limb alignment, presence of chondral lesions, concomitant instability, and body mass index (BMI) need to be considered when contemplating a meniscectomy [12,[16][17][18][19].

Why Repair?
Both the medial and the lateral menisci are important stabilizers and proprioceptors of the knee [26,27].Meniscectomy alters these properties and results in elevated contact pressure in the femorotibial compartment, directly related to the extent of meniscal tissue removal [28][29][30][31][32].It also disrupts knee kinematics and stability [21,33,34], promoting cartilage wear and OA progression [35,36].The principle behind meniscal tissue repair is the potential for healing particularly due to the rich vascularization in the red-red zone and partly in the red-white zone of the meniscus.
Various methods for meniscal repair have been developed, including all-inside, out-in, and in-out techniques [37,38].The selection of the best approach among these depends on the nature and location of the meniscal injury, along with the surgeon's preference.When assessing the outcomes of meniscal repair, it is crucial to consider the specifics of the technique and devices used, the nature of the lesion, its location, and the characteristics of the population examined.The failure rate may also vary depending on the definition of failure adopted by different authors.Consequently, meniscal repair failure rates are highly variable in the literature [15,[39][40][41][42][43].Duethman et al. [15] reported a non-statistically significant difference in failure and reoperation rates between meniscal repair and meniscectomy groups.Conversely, Paxton et al. [43] reported a higher failure rate for meniscal repair.On the other hand, other authors [44][45][46] reported significant improvements in patient outcomes following meniscal repair compared to meniscectomy.Table 1 depicts the main studies comparing the results of meniscectomy versus meniscal repair [15,42,43,[47][48][49][50][51][52].In the authors' opinion, the current failure rates of meniscal repair are unsatisfactory and need to be improved.However, surgeons should not be discouraged from performing meniscal repairs.When a repair fails, it is often possible to perform a new repair or a meniscectomy, which is usually less invasive than what would have been required initially.This approach allows for excellent long-term clinical outcomes even after the failure of a meniscal repair requiring revision [53].Hagmeijer et al. [53] reported zero cases of failure after revising a meniscal repair at a mean follow-up of 17.6 years.Similarly, D'Ambrosi et al. [50] reported a return to sport rate of over 80% in a population of professional athletes.The causes of failure after meniscectomy include persistent pain, instability, and chondrolysis, complications that are challenging to manage and may necessitate more aggressive interventions such as a new meniscectomy, osteotomy, or osteochondral or meniscal allograft implantation.In contrast, the most common causes of failure after repair are nonspecific pain and suture failure, which can be more easily managed with a new repair or partial meniscectomy [50].However, the failure rate of repairs remains high, particularly within one year after surgery [42,53].Complex and bucket handle tears have the highest failure rates at 80% and 47%, respectively, while isolated meniscal lesions have a failure rate of 18.2% [53].Isolated repair has a higher failure rate than meniscal repair with concomitant anterior cruciate ligament reconstruction (ACLr) [43,[54][55][56][57][58].A recent meta-analysis examining meniscal repair outcomes in 3829 patients with a minimum follow-up of two years documented an overall failure rate of 14.8%, which dropped to 8.5% in the presence of a concomitant ACLr [59].Furthermore, medial meniscus repair tends to fail more often than lateral meniscus repair, while partial lateral meniscectomy has a higher reintervention rate compared to partial medial meniscectomy [43,50].Recent data report failure rates of 6.1% and 10.8% for repairs of the lateral and medial meniscus, respectively.Repairs in adults do not have lower failure rates compared to younger people, indicating that advanced age does not adversely affect the failure rate.Therefore, it is not contraindicated to perform meniscal repair in patients over the age of 40 [39,54,56,[60][61][62].Although there is no consensus, Wouters et al. [63] recently reported that repairing a meniscal injury within three weeks of injury reduces the failure rate.Most failures occur in the first year due to impaired healing or reinjury [40,53].The implementation of an early range of motion and immediate postoperative weightbearing does not appear to negatively impact the likelihood of clinical success following meniscal repair [64].Key data on meniscal repair failure rates are summarized in Tables 2 and 3.  Abbreviations: LM = lateral meniscus, LOE = level of evidence; MM = medial meniscus.
However, biological healing time should be respected before returning to sport, which should not be early in the case of meniscal repair, especially in the young population.The current challenge is to lower the failure rate of a meniscal repair.Several techniques have been described to promote meniscal healing after repair.

Meniscal and Biological Augmentation
Over time, various techniques have been developed to enhance the chances of successful meniscal healing.The most common augmentation techniques for meniscal repair are shown Figure 1 and summarized in Table 4.
Abbreviations: LM = lateral meniscus, LOE = level of evidence; MM = medial meniscus; MMPRT = medial meniscus posterior root tears, NS = not specified.However, biological healing time should be respected before returning to sport, which should not be early in the case of meniscal repair, especially in the young population.The current challenge is to lower the failure rate of a meniscal repair.Several techniques have been described to promote meniscal healing after repair.

Meniscal and Biological Augmentation
Over time, various techniques have been developed to enhance the chances of successful meniscal healing.The most common augmentation techniques for meniscal repair are shown Figure 1 and summarized in Table 4.

Trephination
Trephination is a straightforward technique wherein a spinal needle is arthroscopically used to drill holes in the red-red zone, creating multiple channels to divert blood flow from a vascularized area to a less vascularized area.This allows growth factors and cells to reach the meniscal lesion, stimulating fibrous scar formation and its remodeling into fibrocartilaginous tissue [69,70].Experimental studies on animals [70][71][72] have shown that trephination increases vascularization and improves tissue healing.In humans, this translates into enhanced clinical outcomes when trephinations are added to meniscal repair [73,74].However, the effectiveness of trephinations as an isolated procedure is still debated [72].

Abrasion
Abrasion of the margins of the meniscal lesion and the parameniscal synovium can be performed using a shaver or rasp.This easy and fast mechanical stimulation elicits a damage response with the release of growth factors and cytokines that trigger a process of revascularization and healing [75,76].Rasping the parameniscal synovium and abrading the tear edges seem to yield superior results compared to fibrin clots in murine [77] and rabbit models [78].Excellent healing rates in humans have been reported after abrasion combined with meniscal repair, and further confirmed at arthroscopic second looks, although their effectiveness seems to be reduced in the case of tears in poorly vascularized zones [79][80][81].

Microfracture
A lower failure rate of a meniscal repair in case of concomitant ACLr is well documented [43,[54][55][56][57][58]82], theoretically due to the release of mesenchymal stromal cells and growth factors from the bone tunnels [72,73], promoting angiogenesis, matrix synthesis, and cell proliferation [83][84][85].Microfracture of the intercondylar notch aims to simulate this mechanism by creating holes that penetrate the subchondral bone, releasing marrow elements into the joint.Several studies have demonstrated the efficacy and safety of microfractures as an adjunctive technique to meniscal repair [86][87][88], with some authors even speculating on an efficacy superimposed on that obtained by concomitant ACLr [89].A level I randomized controlled trial by Kaminski et al. demonstrated a 100% healing rate in 23 patients after vertical complete meniscal lesion repair when 6 to 7 microfracture holes into the lateral aspect of the intercondylar notch were performed using a special device [90].A recent systematic review showed that bone marrow stimulation reduces the likelihood of failure in patients undergoing isolated meniscal repair, although it does not lead to improvements in knee symptom scores [91].However, clinical results remain contradictory [92], thus questioning its broader applicability [93].

Platelet-Rich Plasma
Different protocols for platelet-rich plasma (PRP) use exist, inevitably affecting results as PRP can be used in single or multiple administrations, in the joint or directly inside the repaired meniscal lesion, as well as on biological supports such as scaffolds or clots.Various preparation techniques lead to multiple types of qualitatively different products.In vitro and in vivo studies support the benefits of PRP augmentation to meniscal repair [94][95][96][97][98].This is also supported by human clinical studies [99][100][101][102], although results may be conflicting [103,104].Despite the difficulties in demonstrating the theoretical preclinical benefits of PRP even in humans [95], Kaminski et al. [105] in their level I RCT demonstrated that injecting PRP into the meniscal lesion after repair improves the rate of healing and clinical outcomes.Otherwise, multiple intra-articular injections of PRP do not appear to have any clinical or healing advantage over its non-use [41].A recent systematic review and meta-analysis of six comparative studies employing PRP augmentation in conjunction with meniscal repair emphasized the biological power of PRP and supported its use as an adjuvant to meniscal healing [106].This point was also highlighted by the systematic review of Haunschild et al. [107], which argued that PRP augmentation may have the potential to decrease the failure rate after meniscal repair.However, PRP may not improve knee symptom scores [91], although results from a recent systematic review reported mixed results [92,93].

Fibrin Clot
A fibrin clot (FC) is an autologous derivative of a patient's peripheral blood.It contains growth factors and cytokines which provide both local chemotactic and mitogenic stimuli for cellular repair, triggering the formation of a fibrous connective tissue scar which remodels over time, potentially healing the meniscal tear [108][109][110][111][112][113].It has been added to meniscal repair with documented good healing rates and clinical results, even in the case of degenerative lesions [114][115][116][117]. Nakanishi et al. [118] showed that during a two-week observation period, there were no significant differences between an FC and platelet-rich fibrin (PRF) clot in terms of the cumulative amount and pattern of growth factor release.Although FC is cheaper and faster to produce than a PRF clot, its application is more technically demanding, invasive, and time-consuming compared to other simpler techniques such as rasping, trephinations, and microfractures.The superiority of FC over these techniques has not been conclusively demonstrated [77], and a recent systematic review considered the current evidence on FC insufficient to draw definitive conclusions on its actual usefulness [93].

Future Perspectives
Although several biological augmentation techniques have been introduced to improve meniscal healing rates, the overall quality of the evidence remains low.The strategies employed are significantly heterogeneous, and the underlying mechanisms are not yet fully understood [69,80,83].Nonetheless, novel approaches, including both intraarticular and extraarticular systemic strategies, are under investigation [91][92][93].Among these, stimulating endogenous irisin release could potentially enhance meniscal repair.Irisin, a myokine physiologically released by skeletal muscle during physical exercise, has been shown in previous studies to exert both paracrine and endocrine effects on various musculoskeletal tissues, including cartilage [128], tendon [129], and intervertebral disc [130].By potentially stimulating meniscal healing, dedicated physical therapy protocols designed to increase endogenous irisin production could be implemented following postoperative repair.However, these theories remain speculative and require preclinical validation.

Figure 1 .
Figure 1.The main techniques to perform biological augmentation of repaired meniscal tears include trephination (A), abrasion (B), microfracture (C), and the administration of platelet-rich

Figure 1 .
Figure 1.The main techniques to perform biological augmentation of repaired meniscal tears include trephination (A), abrasion (B), microfracture (C), and the administration of platelet-rich plasma, fibrin clots, or platelet-rich fibrin clots (D).These can be delivered directly into the repaired tear or injected into the knee joint after surgery.Created with BioRender.com.

Table 1 .
Studies comparing outcomes of meniscectomy versus meniscal repair.

Table 2 .
Systematic reviews and meta-analyses reporting reoperation or overall failure rates of meniscal repair.

Table 3 .
Level III and IV clinical studies reporting reoperation or overall failure rates of meniscal repair.

Table 3 .
Level III and IV clinical studies reporting reoperation or overall failure rates of meniscal repair.

Table 4 .
Main characteristics of the most common augmentation techniques for meniscal repair.